一个与基底膜相关的新型基因特征可用于预测肺腺癌的预后。
A novel basement membrane-related gene signature for prognosis of lung adenocarcinomas.
机构信息
Department of Thoracic and Maxillofacial Surgery (B7X), Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang Province, China.
Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi Province, China.
出版信息
Comput Biol Med. 2023 Mar;154:106597. doi: 10.1016/j.compbiomed.2023.106597. Epub 2023 Jan 24.
BACKGROUND
Lung adenocarcinoma (LUAD) remains a global health concern with its poor prognosis and high mortality. Whether tumor cells invade through the basement membrane (BM) is the key factor to determine the prognosis of LUAD. This study aimed to identify the BM-related gene signatures to improve the overall prognosis of LUAD.
MATERIALS & METHODS: A series of bioinformatics analyses were conducted based on TCGA and GEO datasets. Unsupervised consistent cluster analysis was performed, and 500 LUAD patients were assigned to two different groups according to expressions of 222 BM-related genes. The differentially expressed genes (DEGs) between the two clusters were identified, and Lasso regression, ROC curve, univariate and multivariate Cox regression analyses and enrichment analysis were conducted. Besides, ssGSEA, CIBERSORT and ESTIMATE algorithmwere were employed to understand the relationship between the tumor microenvironment (TME) and risk scores. Moreover, single cell clustering and trajectory analyses were performed to further understand the significance of BM-related genes. Finally, qRT-PCR was used to verify the prognosis model.
RESULTS
A total of 31 prognostic BM-related genes were determined for LUAD, and a novel 17-mRNA prognostic model named BMsocre was successfully established to predict the overall survival of LUAD patients. The high BMscore group indicated worse prognosis. Seventeen DEGs were enriched mainly in metabolism, ECM-receptor interaction and immune response. In addition, the high-risk group showed higher TMB and lower immune score. The low-risk group had a better immunotherapeutic response where immune escape was less likely. The BMscore model was verified in our patient cohort. Furthermore, NELL2 was mainly expressed in clusters of T cells, and was identified to play a critical role in T-cell differentiation.
CONCLUSIONS
A novel BMscore model was successfully established and might be effective for providing guidance to LUAD therapy.
背景
肺腺癌（LUAD）仍然是一个全球性的健康问题，其预后不良，死亡率高。肿瘤细胞是否通过基底膜（BM）侵袭是决定 LUAD 预后的关键因素。本研究旨在确定与 BM 相关的基因特征，以改善 LUAD 的总体预后。
材料与方法
基于 TCGA 和 GEO 数据集进行了一系列生物信息学分析。进行了无监督一致性聚类分析，根据 222 个 BM 相关基因的表达，将 500 名 LUAD 患者分为两个不同的组。鉴定两个聚类之间差异表达的基因（DEGs），并进行 Lasso 回归、ROC 曲线、单因素和多因素 Cox 回归分析和富集分析。此外，还采用 ssGSEA、CIBERSORT 和 ESTIMATE 算法来了解肿瘤微环境（TME）与风险评分之间的关系。此外，还进行了单细胞聚类和轨迹分析，以进一步了解 BM 相关基因的意义。最后，使用 qRT-PCR 验证了预后模型。
结果
确定了 31 个与 LUAD 相关的预后 BM 相关基因，并成功建立了一个新的 17 个 mRNA 预后模型，命名为 BMsocre，用于预测 LUAD 患者的总生存率。高 BMscore 组提示预后较差。17 个 DEGs 主要富集在代谢、ECM-受体相互作用和免疫反应中。此外，高危组具有更高的 TMB 和更低的免疫评分。低危组具有更好的免疫治疗反应，免疫逃逸的可能性较低。BMscore 模型在我们的患者队列中得到了验证。此外，NELL2 主要在 T 细胞群中表达，并被确定在 T 细胞分化中起关键作用。
结论
成功建立了一种新的 BMscore 模型，可能对 LUAD 治疗提供有效指导。
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